title: Cytochrome P450 drives a HIF-regulated behavioral response to reoxygenation by C. elegans.
abstract: Oxygen deprivation followed by reoxygenation causes pathological responses in many disorders, including ischemic stroke, heart attacks, and reperfusion injury. Key aspects of ischemia-reperfusion can be modeled by a Caenorhabditis elegans behavior, the O2-ON response, which is suppressed by hypoxic preconditioning or inactivation of the O2-sensing HIF (hypoxia-inducible factor) hydroxylase EGL-9. From a genetic screen, we found that the cytochrome P450 oxygenase CYP-13A12 acts in response to the EGL-9-HIF-1 pathway to facilitate the O2-ON response. CYP-13A12 promotes oxidation of polyunsaturated fatty acids into eicosanoids, signaling molecules that can strongly affect inflammatory pain and ischemia-reperfusion injury responses in mammals. We propose that roles of the EGL-9-HIF-1 pathway and cytochrome P450 in controlling responses to reoxygenation after anoxia are evolutionarily conserved.
authors.affiliation: Howard Hughes Medical Institute, Department of Biology, McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Dengke K
authors.initials: DK
authors.lastname: Ma
authors.forename: Michael
authors.initials: M
authors.lastname: Rothe
authors.forename: Shu
authors.initials: S
authors.lastname: Zheng
authors.forename: Nikhil
authors.initials: N
authors.lastname: Bhatla
authors.forename: Corinne L
authors.initials: CL
authors.lastname: Pender
authors.forename: Ralph
authors.initials: R
authors.lastname: Menzel
authors.forename: H Robert
authors.initials: HR
authors.lastname: Horvitz
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D015777:Eicosanoids / Q000378:metabolism; D019143:Evolution, Molecular; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; C403074:Egl-9 protein, C elegans; D015777:Eicosanoids; D005231:Fatty Acids, Unsaturated; D051793:Hypoxia-Inducible Factor 1; D010100:Oxygen